The project's long-term objective is to enhance understanding of the controls regulating cell cycle progression in eukaryotic cells. The investigations will focus on fission yeast weel+ gene product, a novel protein kinase which phosphorylates protein substrates on tyrosine and serine residues, and which plays a key role in the control mechanism inhibiting the induction of M-phase. The specific aims of the project are to: 1. Elucidate the biochemical process by which p107weel protein kinase inhibits the initiation of mitosis. The aim is to identify the critical in vivo substrates of p107weel kinase. Sites of phosphorylation will be mapped, and the functional consequences of phosphorylation will be evaluated. 2. Understand how p107weel activity is regulated. These studies seek to define the relationship between structure and function of p107weel kinase. A major goal will be to map the sites of p107weel which are phosphorylated and to mutate those sites in order to appraise the functional importance of phosphorylation. 3. Identify and characterize new mitotic control elements: the swo genes. Three new genes involved in M-phase inhibition control pathway have been cloned. Two appear to be involved in preventing premature chromosome condensation, whilst the third is required to prevent uncontrolled mitotic induction. The structure and function of the proteins encoded by these genes will be analyzed. The proposed studies will provide important insights into the general properties of eukaryotic cell cycle control, and offer a valuable framework for the investigation of cell cycle controls operating in complex multicellular organisms. The controls form the underlying mechanism by which cell division is regulated. Therefore, elucidation of cell cycle control processes will greatly aid the rational investigation and treatment of human diseases related to cell proliferation abnormalities.